title: FGF/MAPK/Ets signaling renders pigment cell precursors competent to respond to Wnt signal by directly controlling Ci-Tcf transcription.
abstract: FGF and Wnt pathways constitute two fundamental signaling cascades, which appear to crosstalk in cooperative or antagonistic fashions in several developmental processes. In vertebrates, both cascades are involved in pigment cell development, but the possible interplay between FGF and Wnt remains to be elucidated. In this study, we have investigated the role of FGF and Wnt signaling in development of the pigment cells in the sensory organs of C. intestinalis. This species possesses the basic features of an ancestral chordate, thus sharing conserved molecular developmental mechanisms with vertebrates. Chemical and targeted perturbation approaches revealed that a FGF signal, spreading in time from early gastrulation to neural tube closure, is responsible for pigment cell precursor induction. This signal is transmitted via the MAPK pathway, which activates the Ci-Ets1/2 transcription factor. Targeted perturbation of Ci-TCF, a downstream factor of the canonical Wnt pathway, indicated its contribution to pigment cell differentiation Furthermore, analyses of the Ci-Tcf regulatory region revealed the involvement of the FGF effector, Ci-Ets1/2, in Ci-Tcf transcriptional regulation in pigment cell precursors. Our results indicate that both FGF and the canonical Wnt pathways are involved in C. intestinalis pigment cell induction and differentiation. Moreover, we present a case of direct transcriptional regulation exerted by the FGF signaling cascade, via the MAPK-ERK-Ets1/2, on the Wnt downstream gene Ci-Tcf. Several examples of FGF/Wnt signaling crosstalk have been described in different developmental processes; however, to our knowledge, FGF-Wnt cross-interaction at the transcriptional level has never been previously reported. These findings further contribute to clarifying the multitude of FGF-Wnt pathway interactions.
authors.affiliation: Cellular and Developmental Biology Laboratory, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Napoli, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Squarzoni
authors.forename: Fateema
authors.initials: F
authors.lastname: Parveen
authors.forename: Laura
authors.initials: L
authors.lastname: Zanetti
authors.forename: Filomena
authors.initials: F
authors.lastname: Ristoratore
authors.forename: Antonietta
authors.initials: A
authors.lastname: Spagnuolo
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002938:Ciona intestinalis; D024202:Electrophoretic Mobility Shift Assay; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D017403:In Situ Hybridization; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050784:Proto-Oncogene Protein c-ets-1; D051153:Wnt Proteins; D005346:Fibroblast Growth Factors; D020928:Mitogen-Activated Protein Kinases